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The court found that a different interpretation could result in marketing exclusivity for the original innovator drug in perpetuity.

In Otsuka Pharmaceutical Co. v. Burwell, the U.S. District Court for the District of Columbia agreed with the Food and Drug Administration’s (FDA’s) interpretation that the three-year clinical investigation exclusivities set forth in 21 U.S.C. §§ 355(c)(3)(E) (iii) and (iv) prohibit the approval of second-in-time applications for a drug with the same “active moiety” as the drug with the exclusivity.1

Otsuka Pharmaceutical Company asserted that the FDA improperly approved Alkermes, Inc.’s application under 21 U.S.C. § 355(b)(2) for Aristada (aripiprazole lauroxil) prior to the expiration of Otsuka’s three-year clinical investigation exclusivity periods that were awarded to its Abilify Maintena (aripiprazole) product.2 Abilify Maintena was awarded an initial three-year exclusivity period upon the submission of a new drug application that included new clinical investigations demonstrating the safety and efficacy of Abilify Maintena, which is an extended-release injectable suspension of aripiprazole.3 Abilify Maintena was awarded another three-year exclusivity period upon the submission of a supplemental new drug application that included new clinical investigations demonstrating the safety and efficacy of Abilify Maintena for treating adult patients with schizophrenia experiencing an acute relapse — a new indication.4

Alkermes submitted a new drug application under 21 U.S.C. § 355(b)(2) (or 505(b)(2) Application) for its drug Aristada.5 Aristada is an extended-release injectable suspension of aripiprazole lauroxil. Aripiprazole lauroxil is a prodrug; that is, after its administration, it is metabolized in the body into N-hydroxymethyl aripiprazole (which is a prodrug of aripiprazole).6 Under the FDA’s chemistry-based approach, the active moiety of aripiprazole lauroxil is N-hydroxymethyl aripiprazole, as this is the remaining molecule or ion — excluding any ester, salt or other non-covalent derivatives.7 Accordingly, the active moiety of Abilify Maintena is aripiprazole, and the active moiety of Aristada is N-hydroxymethyl aripiprazole. Alkermes’ 505(b)(2) Application for Aristada did rely on investigations conducted by and sponsored by Otsuka for its original Abilify tablets; however, it did not rely on any of the new clinical studies conducted by Otsuka for its Abilify Maintena product.8

Otsuka alleged that the FDA was prohibited from approving Aristada prior to the expiration of the three-year exclusivity periods for Abilify Maintena because, even though both the active ingredients and the active moieties were different, Aristada’s application was for the same conditions of approval (i.e., “treatment of schizophrenia using a once-monthly, long-acting injectable formulation of aripiprazole”), and further treated the condition in a similar way and relied on similar clinical trials.9

The FDA disagreed, stating that the exclusivity provisions do not bar a second-in-time drug application if the drug with exclusivity and the drug for which approval is being sought have different active moieties.10 Following the two-step framework of Chevron,11 the district court agreed and ultimately found that the FDA’s interpretation of the statute was reasonable and permissible.12 The court noted that, “[f]or approximately two decades now, the FDA has focused on the active moiety of a drug—i.e., the molecule or ion, excluding [certain appended portions of the molecule,] responsible for the physiological or pharmacological action of the drug substance—to identify and distinguish different drugs . . . .”13 The court also agreed with the FDA that

requiring that the exclusivity benefit be limited based on the active moieties of the relevant drugs—such that it is deemed to block only second-in-time drug applications that, in effect, concern the same drug—encourages innovation by guarding against approval of drugs with the same active moiety for the same exclusivity-protected use, and simultaneously promotes market competition by ensuring that this exclusivity does not block approval of drugs with different active moieties that may have some advantages over previously approved active moieties. To be sure, one might imagine a bigger (or smaller) exclusivity bar than the "active moiety" approach permits, but, at the end of the day, the myriad ambiguities in the relevant statutory language makes clear to this Court that striking the desired balance between an innovator with an expansive exclusivity benefit (on the one hand) and a host of stifled future potential competitors (on the other) was a policy choice that Congress intended the FDA to make.14

The court noted that, while it may be unfair to allow a second-comer to reference and rely on the innovator’s studies for aripiprazole to obtain approval of a long-acting formulation of aripiprazole while avoiding the exclusivity awarded to that same innovator following its required work for a long-acting formulation, a different interpretation could result in marketing exclusivity for the original innovator drug in perpetuity.15 Thus, the district court condoned the FDA’s interpretation of the three-year clinical investigation exclusivity to be based on an “active moiety” determination.

The material in this publication was created as of the date set forth above and is based on laws, court decisions, administrative rulings and congressional materials that existed at that time, and should not be construed as legal advice or legal opinions on specific facts. The information in this publication is not intended to create, and the transmission and receipt of it does not constitute, a lawyer-client relationship.